Upper limb function changes over 12 months in untreated SMA II and III individuals: an item-level analysis using the...

Area of Science:

• Neurology
• Clinical assessment tools
• Rare disease research

Background:

• The Revised Upper Limb Module (RULM) is widely adopted in clinical trials and practice for assessing upper limb function.
• Understanding natural disease progression is crucial for interpreting treatment effects in clinical trials.

Purpose of the Study:

• To apply 'shift analysis' to longitudinal RULM data from an untreated cohort.
• To characterize patterns of ability loss and gain for each RULM item.
• To stratify findings by spinal muscular atrophy (SMA) type, age, SMN2 copy number, and motor function.

Main Methods:

• Analysis of 222 12-month paired RULM assessments from 129 individuals with SMA.
• Stratification by SMA type (II and III), age, SMN2 copy number, and motor functional status.
• Utilized 'shift analysis' to quantify changes in RULM item performance over time.

Main Results:

• 54% of type II and 29% of type III SMA patients experienced loss of one or more RULM activities.
• 42% of type II and 22% of type III SMA patients gained one or more RULM activities.
• Concomitant gains and losses were observed in 27% of type II and 9% of type III SMA patients.

Conclusions:

• Shift analysis provides a novel method for detecting changes in RULM performance.
• These findings enhance the interpretation of longitudinal data in treated SMA populations.
• Characterizing natural history through RULM item changes is vital for evaluating therapeutic interventions.